Interferon (IFN) is a kind of soluble protein produced by a variety of cells which has many important biological functions, including anti-viral, anti-tumor, and immunoregulatory functions. Interferons can be divided into type I, type II, and type III interferons according to the differences in the types of producing cells, receptors and biological activities etc. Type I IFNs, which are mostly induced by viruses and synthetic double-stranded RNA, are also known as anti-viral interferons. There are three forms of type I interferons: IFNα, INFβ, IFNω. Type II IFN, also known as immune interferon or IFNγ, is produced by the T cells, and is an important immunoregulatory factor in vivo. Type III interferon is made up of IFN-λ molecules.
In recent years, many companies in the world have engaged in the research of interferon, as exemplified by a number of pertinent patents and disclosure documents. For example, U.S. Pat. Nos. 4,695,623 and 4,897,471 disclosed new types of human interferon polypeptides which have amino acid sequences containing the common or predominant amino acids found in naturally occurring α-interferon polypeptides. That new type of interferon was named IFN-con (consensus interferon α. The disclosed amino acid sequences were named IFN-con1, IFN-con2 and IFN-con3. Genes encoding IFN-cons and gene expression in Escherichia coli were also disclosed. Compared with leukocyte interferon or other type I interferons, studies have shown that recombinant IFN-con has higher anti-viral, anti-proliferative and natural killer cell activities in vitro.
U.S. Pat. No. 5,372,808 disclosed the use of human IFN-con in the treatment of diseases. Compared with previous clinically approved α-interferon such as Intron® A (IFN-α2b, SGP) produced by Schering-Plough, recombinant human IFN-con has been shown to have lower side-effects. By the end of 1997, the FDA had approved the use of human IFN-con, which was produced by Amgen and sold under the brand name Infergen® (interferon alfacon-1) (SEQ ID NO: 1), for clinical treatment of hepatitis C.
Both U.S. Pat. No. 7,364,724 and Chinese Patent Publication No. CN1740197A (incorporated in their entirety as references to this application) disclosed a recombinant interferon (hereafter referred to as “rSIFN-co” (SEQ ID NO: 1)) that has enhanced efficacy, fewer side-effects and can be used in high doses. The said recombinant interferon has the same amino acid sequence as Infergen® (SEQ ID NO: 1), but has different spatial structure and biological efficacy. In addition, the above-mentioned Chinese Patent Publication No. CN1740197A also disclosed the crystal form of said recombinant interferon and its crystallization method thereof; however, the crystals were of poor quality, had loose internal structures and an X-ray diffraction resolution as low as 5 Å such that they were not suitable for obtaining useful structural information from further analysis of the protein spatial structure. It is of great interest to obtain good quality crystals of the said recombinant interferon with altered structure and functions at high X-ray diffraction resolution so as to determine the three-dimensional structure of said recombinant interferon, establish its model, and take advantage of said structure and model to perform drug design and to improve the efficacy of known interferons.